Anti-CD19-CD3E-CAR-T Cells in Relapsed/Refractory Autoimmune Disease
China6 participantsStarted 2024-04-20
Plain-language summary
This is an investigator-initiated trial to evaluate the safety and efficacy of anti-CD19-CD3E-CAR-T cells in the relapse or refractory autoimmune diseases.
Who can participate
Age range18 Years – 65 Years
SexALL
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Inclusion criteria
✓. Age between 18 and 65 years old (inclusive), regardless of gender.
✓. Positive expression of CD19 on peripheral blood B cells confirmed by flow cytometry.
✓. Functional requirements for major organs are as follows: 1) Bone marrow function must meet: A. Neutrophil count ≥ 1×109/L (no colony-stimulating factor treatment within 2 weeks before examination); B. Hemoglobin ≥ 60g/L; 2) Liver function: Alanine aminotransferase (ALT) ≤ 3×ULN (excluding ALT elevation due to inflammatory myopathy), aspartate aminotransferase (AST)≤3×Upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy), TBIL≤1.5×ULN (or ≤ 3.0×ULN for subjects with Gilbert syndrome); 3) Renal function: creatinine clearance rate (CrCl) ≥ 30ml/minute (calculated by Cockcroft/Gault formula, acute CrCl decrease due to the target disease is excluded); 4) Coagulation function: International standardized ratio (INR) \<1.5×ULN, prothrombin time (PT) \<1.5×ULN; 5) Cardiac function: Stable hemodynamic.
✓. Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
✓. Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
✓. SLE fulfilling the 2019 the American College of Rheumatology (ACR) /European League Against Rheumatism (EULAR) and classification criteria.
✓. Systemic lupus erythematosus disease activity index (SLEDAI)-2000 score ≥ 6 with at least one BILAG (British Isle Lupus Rating Group Index 2004) A or two BILAG B; or SLEDAI-2000 score ≥ 8.
✓. Definition of relapsed/refractory: Conventional treatment over 6 months remains ineffective, or disease recurrence after remission. Definition of conventional treatment: the use of glucocorticoids and cyclophosphamide, and any one or more of the following immunomodulatory drugs: antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics including belimumab, rituximab, and tocilizumab, etc.
Exclusion criteria
✕. Subjects with a history of severe drug allergies or allergic tendencies;
✕. Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections;
✕. Subjects with central nervous system diseases caused by autoimmune diseases or non-autoimmune diseases (including epilepsy, psychosis, organic brain syndrome, cerebral vascular accidents, encephalitis, central nervous system vasculitis);
✕. Subjects with insufficient cardiac function;
✕. Subjects with congenital immunoglobulin deficiencies;
✕. History of malignancy within five years;
✕. Subjects with end-stage renal failure;
✕. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA \>ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing;
What they're measuring
1
The incidence of dose-limiting toxicities (DLTs) (Safety)
Timeframe: Up to 28 days from CAR-T infusion
2
Proportion of patients for whom the desired dose of anti-CD19-CD3E-CAR-T cells can be successfully manufactured
Timeframe: Up to 21 days from apheresis
3
Clinical response for relapsed/Refractory SLE
Timeframe: 12 weeks post CAR-T infusion
4
Clinical response for Sjögren's Syndrome
Timeframe: 12 weeks post CAR-T infusion
5
Clinical response for relapsed/refractory/progressive systemic sclerosis
Timeframe: 12 weeks post CAR-T infusion
6
Clinical response for relapsed/refractory/progressive inflammatory myopathy
Timeframe: 12 weeks post CAR-T infusion
7
Clinical response for relapsed/refractory anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis:
Timeframe: 12 weeks post CAR-T infusion
8
Clinical response for relapsed/refractory/Catastrophic Antiphospholipid Syndrome